Nicotinamide mononucleotide (NMN) ameliorates obesity and improves insulin sensitivity in a mouse model for a female hormonal disorder – polycystic ovary syndrome (PCOS).
Polycystic ovary syndrome (PCOS) – a hormonal disorder that causes infertility and metabolic dysfunction – affects 6% to 12% of women during their reproductive years. Common PCOS-related symptoms include obesity and insulin resistance which can lead to type 2 diabetes and cardiovascular complications. Clinicians recommend diet and exercise and/or pharmaceuticals like metformin to manage PCOS, but about 46% of women find diet and exercise difficult to sustain, and metformin has adverse side effects like nausea.
Now, as published in Molecular Metabolism, Walters and colleagues from the University of New South Wales in Australia show that treating a PCOS mouse model with 2 g/L of NMN ameliorates metabolic symptoms like obesity and insulin resistance and restores muscle NAD+ levels. The findings suggest that NMN, known for having few negative side effects, may reverse the metabolic abnormalities associated with PCOS.
To evaluate how NMN affects metabolic dysfunction in PCOS, Walters and colleagues established a PCOS mouse model by exposing female mice to dihydrotestosterone, a sex hormone. After treating these mice with NMN in their drinking water, the Australian research team measured insulin resistance, a sign of metabolic impairment measured by how much insulin is required to metabolize glucose. PCOS mice exhibited more than twice the amount of insulin needed to metabolize glucose compared to healthy mice, which was mitigated by NMN. These findings suggest that NMN restores insulin resistance in PCOS mice.
To find whether improved insulin sensitivity from NMN ameliorates PCOS-related obesity, Walters and colleagues weighed fat reservoirs called “fat pads,” which are located at multiple locations throughout the body. The investigators measured the weight of five of these fat pads to find that they all weighed more in PCOS mice. However, NMN treatment lowered the weight of all five fat pads. These findings suggest that NMN can help with obesity in PCOS.
Because research has shown that NMN supplementation increases cellular concentrations of the pro-longevity molecule NAD+, the research team examined muscle NAD+ levels. While PCOS mice had about half the muscle NAD+ concentrations of healthy mice, NMN tended to restore these levels, although the restored NAD+ levels were not statistically significant. These findings suggest that increasing NAD+ with NMN could mitigate metabolic dysfunction in PCOS mice. The exact mechanism by which NAD+ may improve metabolic function remains unclear.
“Here, we showed that NAD levels in muscle are strongly reduced in an hyperandrogenized rodent model of PCOS, and that treatment with the NAD precursor NMN can correct this deficit,” said Walters and colleagues. “This restoration of NAD levels in muscle was accompanied by an improvement in a range of metabolic parameters induced by [dihydrotestosterone] treatment.”
Although the study doesn’t demonstrate that NMN can restore infertility in PCOS females, it provides hope that, in addition to lifestyle interventions, NMN can reverse metabolic impairments. Moreover, by improving insulin sensitivity and reducing obesity, NMN may help prevent age-related diseases linked to PCOS like type 2 diabetes and cardiovascular disease. With the multitude of NMN clinical trials underway, this study adds to the plethora of conditions to which NMN may offer a means of treatment.
Model: Female C57Bl6 mice
Dosage: 2 g/L NMN via drinking water for eight weeks